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First published online May 19, 2008
Journal of Experimental Biology 211, 1781-1791 (2008)
Published by The Company of Biologists 2008
doi: 10.1242/jeb.013581

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Inhibitory neurotransmission, plasticity and aging in the mammalian central auditory system

Donald M. Caspary^1,*, Lynne Ling¹, Jeremy G. Turner^1,2 and Larry F. Hughes¹

¹ Southern Illinois University School of Medicine, Springfield, IL 62794, USA
² Illinois College, Jacksonville, IL 62650, USA

View larger version (22K): [in this window] [in a new window]   Fig. 1. A schematic drawing of the ascending auditory pathway in rat. The auditory nerve carries signals from hair cells of cochlea into cochlear nucleus, where acoustic information projects to other brainstem auditory nuclei. Signals from the ventral cochlear nucleus (VCN) travel to the superior olivary complex (SOC), which comprises three important subgroups (LSO, MSO, MNTB) involved in the localization of sound in space. The SOC sends projections primarily to the inferior colliculus (IC), while information from the dorsal cochlear nucleus (DCN) projects directly to the IC. From the IC, auditory messages proceed to the medial geniculate body (MGB, a subregion of thalamus), which in turn projects to the primary auditory cortex (A1), located in the temporal lobe of cerebrum.

View larger version (16K): [in this window] [in a new window]   Fig. 2. Comparison of age-related hair cell loss and changes in auditory brainstem response (ABR) thresholds of FBN and F344 rats. (A) Cochleograms of aged F344 (24 months, N=8) and aged FBN (32 months, N=7) rats showing percent hair cells relative to young rats. The pattern of age-related hair cell loss was different between the two strains. Aged FBN rats lost few inner hair cells (IHCs), while aged F344 rats displayed small IHC losses (<10%) throughout the cochlea with pronounced increase in IHC loss near the basal end. F344 exhibited U-shaped loss of outer hair cells (OHCs) with the greatest losses (as high as 70%) confined to apical and basal turns. Low levels of OHC losses were observed throughout the F344 cochlea. FBN rats had significant OHC losses starting at the apex, which tapered to moderate losses in the basal regions. The pattern of OHC loss resembles those described for Brown Norway spiral ganglion cells (Keithley et al., 1992). (B) ABR thresholds for young and aged F344 (3 months, N=28; 24 months, N=18) and FBN rats (4 months, N=11; 32 months, N=10) are shown. F344 rat thresholds were lower at 4 and 8 kHz than 16 and 24 kHz. FBN rats displayed a significantly different threshold pattern, with the lowest thresholds at higher frequencies (ANOVA, *P<0.01). Aging affected both strains similarly with near parallel upward threshold shifts. For the FBN strains, age-related threshold shifts did not correlate with the apical pattern of hair cell loss. (Adapted from Turner and Caspary, 2005.)

View larger version (9K): [in this window] [in a new window]   Fig. 3. The effects of aging on protein levels of GABAA receptor subunit 1, β2 and 1 in the IC of FBN and F344 rats. The y-axis represents subunit protein percentage difference from young adult animals (3–4 months) of middle aged (18–20 months) and aged (28–32 months) in rat IC. Note that GABAA receptor 1 subunit protein significantly increased in aged rats of both FBN and F344. While significantly decreased 1 subunit protein was found in the IC of aged FBN rats, it was not found in aged F344 rats (*P<0.05). (Modified from Caspary et al., 1999.)

View larger version (19K): [in this window] [in a new window]   Fig. 4. GABA (10 nmol l–1–10 mmol l–1) modulation of 3[H]-TBOB (t-butylbicycloorthobenzoate) binding in the CIC of young and aged F344 rats. The dose–response curve is shifted to the left. These data have functional implications since the aged GABAA receptor must be more sensitive to GABA than the young GABAA receptor for the channel to be open allowing TBOB to bind to the picrotoxin binding site. (Modified from Milbrandt et al., 1996.)

View larger version (44K): [in this window] [in a new window]   Fig. 5. FBN rat layer V neurons exhibit two major types of receptive field maps. (A) 32% showed the classic V/U-shape with young and aged neurons showing similar responses to current pulse stimulation (not shown). (B) 47% of pyramidal neurons demonstrated a more complex, dynamic response map. (C) Aged complex receptive field neurons responded more vigorously than young neurons to 200 ms current pulses, suggesting altered inhibitory control. Such increased excitability to current would be consistent with reduced GAD67 immunostaining around layer V (LV) somata (see insets; scale bars, 5 µm). (Modified from Turner et al., 2005c.)

View larger version (25K): [in this window] [in a new window]   Fig. 6. Age-related changes of GAD67 message and protein levels in A1 and parietal cortex (PtA) of middle-aged and aged FBN rats compared to young adult rats. (A) Significant age-related changes in GAD67 message levels were seen across all layers of A1 in middle-aged and aged FBN rats (except layer IV of middle-aged A1). Significant GAD67 message decreases within PtA occurred only in the aged group. (B) Whereas all layers of middle-aged and aged A1 showed significant age-related decreases in GAD67 protein, in PtA GAD67 protein levels showed no age-related decreases except in layer IV of middle-aged and aged, and in middle-aged layer VI (*P<0.05). (Modified from Ling et al., 2005.)